Adeno Associated Virus
Adeno-associated virus (AAV) is a small, non-pathogenic virus that has gained attention for its potential as a gene therapy vector. AAV is able to infect both dividing and non-dividing cells, making it a promising tool for delivering therapeutic genes into target cells. Its ability to integrate into the host genome and its low immunogenicity make it a valuable candidate for gene therapy applications.
3 Key excerpts on "Adeno Associated Virus"
eBook - ePub- Rajesh V. Thakker, Michael P. Whyte, John Eisman, Takashi Igarashi, Rajesh V. Thakker, Michael P. Whyte, John Eisman, Takashi Igarashi(Authors)
- 2017(Publication Date)
- Academic Press(Publisher)
...particles. Science. 1965 ; 149 : 754 – 756. 20. Kotterman MA, Schaffer DV. Engineering adeno-associated viruses for clinical gene therapy. Nat Rev Genet. 2014 ; 15 : 445 – 451. 21. Büning H, Nicklin SA, Perabo L, Hallek M, Baker AH. AAV-based gene transfer. Curr Opin Mol Ther. 2003 ; 5 : 367 – 375. 22. Wu Z, Asokan A, Samulski RJ. Adeno-associated virus serotypes: vector toolkit for human gene. therapy. Mol Ther. 2006 ; 14 : 316 – 327. 23. Nakai H, Yant SR, Storm TA, Fuess S, Meuse L, Kay MA. Extrachromosomal recombinant adeno-associated virus vector genomes are primarily responsible for stable liver transduction in vivo. J Virol. 2001 ; 75 : 6969 – 6976. 24. Rosas LE, Grieves JL, Zaraspe K, La Perle KM, Fu H, McCarty DM. Patterns of scAAV vector insertion associated with oncogenic events in a mouse model for genotoxicity. Mol. Ther. 2012 ; 20 : 2098 – 2110. 25. Podsakoff G, Wong KK, Chatterjee S. Efficient gene transfer into nondividing cells by adeno-associated virus-based vectors. J Virol. 1994 ; 68 : 5656 – 5666. 26. Choi J-H, Yu N-K, Baek G-C, et al. Optimization of AAV expression cassettes to improve packaging capacity and transgene expression in neurons. Mol Brain. 2014 ; 7 : 17. 27. McCarty DM. Self-complementary AAV vectors; advances and applications. Mol. Ther. 2008 ; 16 : 1648 – 1656. 28. Escors D, Breckpot K. Lentiviral vectors in gene therapy: their current status and future potential. Arch Immunol Ther Exp (Warsz). 2010 ; 58 : 107 – 119. 29. Katz RA, Skalka AM. The retroviral enzymes. Annu Rev Biochem. 1994 ; 63 : 133 – 173. 30. Coil DA, Miller AD. Phosphatidylserine is not the cell surface receptor for vesicular stomatitis virus. J...
eBook - ePubTranslating Gene Therapy to the Clinic
Techniques and Approaches
- Jeffrey Laurence, Michael Franklin, Jeffrey Laurence, Michael Franklin(Authors)
- 2014(Publication Date)
- Academic Press(Publisher)
...Relatively less progress has been made in addressing the challenge of humoral immunity to AAV, which arises both from the natural infection with the wild-type virus and the administration of the recombinant vector. To date, the approach to anti-AAV neutralizing antibodies has been to exclude seropositive subjects from enrollment in clinical trials, a strategy far from being ideal because it prevents up to 60% of subjects from accessing gene therapy treatment with AAV vectors. Ongoing and future efforts toward a deeper understanding of immune responses to AAV and toward the development of safe and effective strategies to modulate these responses will help further broaden the scope of in vivo gene transfer with AAV vectors. Keywords Adaptive immunity; Adeno-associated virus vector; Clinical trial; Gene therapy; Innate immunity List of Abbreviations AAV Adeno-associated virus AAP Assembly activating protein BLyS B-lymphocyte stimulator EGFR Epidermal growth factor receptor FGFR Fibroblast growth factor receptor HGFR Hepatocyte growth factor receptor HSPG Heparan sulfate proteoglycan hNPCs Human non-parenchymal liver cells ITRs Inverted terminal repeats IFNs Interferons KCs Kupffer cells LN Lupus nephritis LSECs Liver sinusoidal endothelial cells MVM Minute virus of mice NAbs Neutralizing antibodies NHP Nonhuman primates NPC Nuclear pore complex PAMPs Pathogen-associated molecular patterns PBMC Peripheral blood mononuclear cells pDCs Plasmacytoid dendritic. cells PDGFR Platelet-derived growth factor receptor PLA Phospholipase PRR Pattern recognition receptors TLRs Toll-like-receptors 4.1. Introduction The goal of gene therapy for inherited diseases is the long-term correction of the disease phenotype in affected patients...
eBook - ePub- Phoebe Lostroh(Author)
- 2019(Publication Date)
- Garland Science(Publisher)
...The vector causes T cells to express a herpesvirus thymidine kinase gene (Figure 16.32). The gene is therapeutic because the herpesvirus thymidine kinase enzyme turns the pharmaceutical acyclovir into toxic metabolites that kill the cells expressing the herpesvirus thymidine kinase. If a patient transplanted with transformed cells and shows signs of GVHD, ganciclovir can be used to kill the problematic T cells. Figure 16.32 Cells transformed with the vector express herpesvirus thymidine kinase. Patients who receive bone marrow from a related but not identical donor can develop graft-versus-host disease (GVHD), caused by CD8 + T cells derived from the donated stem cells. To prevent GVHD, the donor cells are transformed ex vivo so that CD8 + T cells from the donor stem cells express herpesvirus thymidine kinase. After transplantation, the recipient is treated with acyclovir to kill CD8 + T cells from the donor, which would otherwise cause GVHD. An example of an approved gene therapy based on adeno-associated virus (AAV), a type of parvovirus, is alipogene tiparvovec. Adeno-associated viruses have ssDNA genomes and are called satellite viruses because they cannot replicate in the absence of co-infection with another virus such as adenovirus or herpesvirus (see Chapter 17). Instead, in the absence of co-infection, the host converts their small (< 5 kb) genomes into dsDNA that enters the nucleus and persists as an episome, where genes can be expressed but the genome cannot direct lytic reproduction without a helper virus. Gene therapy vectors derived from AAV are advantageous compared with retroviruses in that the DNA never inserts into a host chromosome, minimizing the risk of the therapy itself causing cancer. Alipogene tiparvovec treats familial lipoprotein lipase deficiency, a metabolic disorder that disrupts normal processing of fats and causes severe inflammation of the pancreas, leading to repeated hospitalizations and excruciating pain...
